Encyclopedia of drug metabolism and interactions

摘要: VOLUME I Part 1: Basics Overview of Drug Metabolism Chapter 1 Review in Discovery and Development 2 Reactions Models 3 Enzyme kinetics drug metabolism reactions drug-drug interactions 4 Developmental changes metabolizing enzymes 5 Species differences II: systems involved animals humans 6 Structure function cytochrome P450 7 Mechanism mediated 8 Transcriptional regulation 9 Cytochrome polymorphisms 10 Flavin monooxygenase 11 Molybdenum containing 12 Amine odidases reductases 13 Epoxide hydrolase 14 Esterases amidases 15 UDP- glucuronosyltransferases 16 Sulfotransferases 17 Glutathione S- transferases 18 Amino acid conjugation II III: General principals ADME. transporters other mechanisms transport Introduction to Anatomical Physiological Parameters that Influence Gastrointestinal Absorption drugs into the body principles distribution ABC their impact on disposition/drug sensitivity resistance SLC family Systems where occurs Mass balance studies Bioavailability bioequivalence Allometric scaling Effect protein binding ADME Excretion Pharmacokinetics (PK) toxicokinetics (TK) Experimental design/mathematical models data analysis/interpretation for PK /TK Physiologically-Based Pharmacokinetic Modeling Pharmacodynamics Interrelationships between / IV: some specific groups delivery 19 herbal dietary constituents 20 anticancer 21 cardiovascular 22 biological 23 natural toxins 24 pregnant mother/placenta/fetus III V: Design development Where when does enter as a concern? Challenges frontloading toxicity testing anti- cancer discovery Role selection new candidates Efficient development. How speed up process Metabolite profiling identification Bioactivation oxidative stress safety evaluation VI: Methods protocols prediction interaction In silico determination enzyme metabolic rates Assays microarrays pathways Applications using Caco-2 cells TC7 vitro liver study induction/inhibition. Prediction vivo Assessing Hepatic Disposition Toxicity Xenobiotics Using Primary Hepatocytes Monoclonal Antibody Based Analyses Human Multifuctional Cytochromes Validation precision- cut slices tool induction Practical aspects high throughput solubility dissolution assessment preformulation Integrated Approaches Blood Brain Barrier its role (not genetically modified) mouse knockout transgenic IV VII: Pharmacology toxicology Introduction. Overview. I: Phase (P450) (non P450) Covalent Binding MIST Cell- based predictors Toxicities Metabolites Toxicogenomics Metabonomics Proteomics Stereoselectivity PART VIII: physiological conditions, diseases, drug- food interactions, age, sex, factors effect Genetic influence Drug- Inhibition Interactions 2: Induction Ontogeny Natural Modulators Metabolism: Dietary supplements Clinical Relevance (Food Effects Pharmacology) Idiosyncratic inflammatory (or xenobiotic) hepatotoxicity Regulation Drug-Metabolizingnzymes Transporters Infection, Inflammation, Cancer V IX: Bioanalytical methods studying Importance vivo/in analytical results Walter mass spectrometry: LC-MS, LC-MS/MS, GC-MS Electrospray Infusion nanospray ionization Emerging Atmospheric pressure Matrix assisted laser desorption (MALDI) Ion trap quadrupole MS Hybrid LTQ- FTMS Spectrometry Imaging (MSI) Mobility High Performance Tandem Inductively coupled plasma spectrometry (ICP MS) element- analysis Online Electrochemical LC- Techniques Profiling NMR Whole autography radioactive non- isotope assays Ligand (immunoassays) Direct Analytical method validation accordance regulatory guidelines Leveraging advances HPLC maximize DMPK quality Methodologies Increase Throughput Biomarkers enable PK/PD Bioanalytics Microdosing Reactive Plasma VI X: introduction. DDI Risk Assessment Evaluation Development: Interfacing Current future tools predicting clinical Predicting human biotransformation Conjugation, transport, elimination consequences Glucuronosyltransferases Drug/food drug/herb disease activation treatment outcomes potential XI patient populations psychotropic Metabolic-based polytherapy with AED Oral chemotherapeutic agents: Understanding action pediatric patients Population- pharmacokinetic modeling simulation labeling. The pharmacology recommended dose